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    Overcoming cancer therapy resistance by targeting inhibitors of apoptosis proteins and nuclear factor-kappa B

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    XuLiang_AJTR_1(1)4.pdf (325.1Kb)
    Issue Date
    2008-10-25
    Author
    Dai, Yao
    Lawrence, Theodore S.
    Xu, Liang
    Publisher
    e-Century Publishing
    Type
    Article
    Article Version
    Scholarly/refereed, publisher version
    Published Version
    http://www.ajtr.org/810001A.html
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    Abstract
    Chemo- or radioresistance markedly impairs the efficacy of cancer therapy and involves anti-apoptotic signal transduction pathways that prevent cell death. In resistant cancer cells, both inhibitors of apoptosis proteins (IAPs) and nuclear factor-kappa B (NF-κB) play a pivotal role in preventing apoptosis triggered by a variety of stresses, facilitating them as potential targets in cancer treatment. Furthermore, mounting evidences have established the crosstalks between IAPs (eg. XIAP, cIAP-1, cIAP-2) and proteins involved in NF-κB signaling (eg. TRAF2, RIP1, TAB1). Second mitochondria-derived activator of caspases (Smac) is a mitochondrial protein that released into cytoplasm upon apoptotic stimuli. As Smac functions as an endogenous IAP inhibitor, small molecule Smac-mimetics are believed to neutralize IAPs function that results in liberating caspase activity and promoting apoptosis. Moreover, recent studies show that Smac-mimetics may kill cancer cells in a different manner, which involves inducing ubiquitination of cIAPs, regulating NF-κB signaling and facilitating TNFα- triggered, caspase-8-mediated apoptosis in a certain cancer cell types. In other cancer cells that are resistant to TNFα or chemo/radiotherapy, Smac-mimetic IAP-inhibitors can enhance ionizing radiation or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis, indicating the potential role of Smac- mimetics in overcoming acquired therapy-resistance. Such findings provide important impetus for utilizing IAP- inhibitors as novel adjuvant therapy for the TNFα–resistant, NF-κB constitutively active cancers that account for the majority of patients who are refractory to current therapeutic approaches. (AJTR810001).
    Description
    This is the published version, also available here: http://www.ajtr.org/810001A.html.
    URI
    http://hdl.handle.net/1808/17361
    Collections
    • Molecular Biosciences Scholarly Works [590]
    Citation
    Dai, Yao., Lawrence, Theodore S., Xu, Liang. "Overcoming cancer therapy resistance by targeting inhibitors of apoptosis proteins and nuclear factor-kappa B." (2008) Am J Transl Res 2009;1(1):1-15.

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    785-864-8983

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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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